Cracking the Code of Aging: How IL-11 Inhibition Could Redefine Human Lifespan

 

The desire and quest to enhance human health span and lifespan has been an interesting area of study for a long time. A recent groundbreaking study highlights an intriguing potential strategy: Investigating the regulation of Interleukin-11 (IL-11) protein. IL-11 is an interleukin from the IL-6 family that has a major role in the inflammation and fibrosis of different tissues. IL-11 levels rise with age in all tissues responsible for age-related diseases and deterioration of health.

Aging research has traditionally focused on many well-known factors such as genes, behaviour, or metabolic pathways. However, these have had the following important limitations: Current approaches often target symptoms instead of addressing the root cause of the problem. Furthermore, inflammation and cell aging which are crucial in the aging process, have remained difficult to revert effectively.

The recent study's findings are nothing short of remarkable. It finally turned out that the genetically modified mice that lacked both the IL-11 protein and the Il11ra1 gene were protected from the adverse effects of aging on metabolism, multimorbidity, and frailty. These GM mice also displayed reduced levels of biomarkers related to aging, and enhanced muscle performance. When anti-IL-11 antibodies were given to older mice, the metabolic rates and the ability to move increased, aging parameters were decreased, and the life span was increased by about 24.9% on average.

The findings of the study show that IL-11 inhibition is associated with several fundamental biological processes. The IL-11 upregulation interferes with the ERK-AMPK-mTORC 1 signalling pathway (Figure 1) related to cellular metabolism and growth, thus resulting in metabolic dysfunctions and aging. Preventing the actions of IL-11 is beneficial in reopening this loop. In addition, IL-11 plays a role in chronic inflammation and cellular aging, associated features of aging. Decreasing its levels decreases inflammation and delays aging-related diseases, thus making aging healthier.

Figure 1. Signalling pathway of IL-11

The present work has various practical implications for human health. Anti-IL-11 drugs that are being experimentally used to treat fibrotic lung diseases, which are currently in phase I/II trials and could potentially be explored for their efficacy in the treatment of aging in humans. Thus, the inhibition of IL-11 may offer a feasible approach to increasing human healthspan and lifespan, improving the overall quality of life. Science continues to advance as year by year we inch towards the goal of understanding how to age healthily and the possibilities that this is opening up for interventions to change the way we age.

Reference:

Widjaja AA, Lim WW, Viswanathan S, Chothani S, Corden B, Dasan CM, Goh JW, Lim R, Singh BK, Tan J, Pua CJ. Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. Nature. 2024 Jul 17:1-9. https://doi.org/10.1038/s41586-024-07701-9

Image Credits:

1. Cover Image - https://www.nytimes.com/2024/03/20/well/live/aging-biology-dna.html

2. Figure 1 - https://www.nature.com/articles/s41586-024-07701-9/figures/1